Antimicrobial peptides: features and modes of action

Antimicrobial peptides (AMPs) or host defense peptides are short amphipathic, generally cationic, evolutionarily conserved biomolecules that constitute the first line of defense in most living organisms. These peptides display activity against Gram-negative and Gram-positive bacteria, fungi, and some protozoa and viruses. AMPs can be linear or cyclic; the cyclic structure is achieved through end-to-end ligation or through disulfide bridge(s) between the Cys residues near the termini. Structurally, AMPs can be classified as α-helical, β-sheets, αβ, and non-αβ. Another useful classification could be disulfide-containing and disulfide-lacking peptides. Most AMPs fold into conformations that introduce amphipathicity, a feature that enables them to interact with membranes. Understandably, a large majority of AMPs exhibit antimicrobial activity through membrane-destabilization, which causes leakage of cellular content, thereby causing cell death. Although the exact mechanism of action is an enigma and could be peptide-specific, several models have been proposed for their antimicrobial action. These include the barrel-stave model, the carpet model, the toroidal pore model, and the detergent model. Apart from the antimicrobial activity, AMPs could possess anticancer activity, antimycoplasmal activity, spermicidal activity, cause activation of the immune response, and regulation of inflammation. These attributes of AMPs make them promising candidates as an alternative to conventional antibiotics.